End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
20131938
DOI
10.33549/physiolres.931640
PII: 1640
Knihovny.cz E-resources
- MeSH
- Endothelin A Receptor Antagonists * MeSH
- Endothelin B Receptor Antagonists MeSH
- Antihypertensive Agents pharmacology MeSH
- Atrasentan MeSH
- Bosentan MeSH
- Time Factors MeSH
- Endothelin-1 metabolism MeSH
- Glomerulosclerosis, Focal Segmental genetics metabolism physiopathology prevention & control MeSH
- Heterozygote MeSH
- Homozygote MeSH
- Hypertension complications drug therapy genetics metabolism physiopathology MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Sodium Chloride, Dietary MeSH
- Disease Models, Animal MeSH
- Podocytes drug effects metabolism pathology MeSH
- Rats, Transgenic MeSH
- Disease Progression MeSH
- Pyrrolidines pharmacology MeSH
- Receptor, Endothelin A metabolism MeSH
- Receptor, Endothelin B metabolism MeSH
- Renin genetics MeSH
- Sulfonamides pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Endothelin A Receptor Antagonists * MeSH
- Endothelin B Receptor Antagonists MeSH
- Antihypertensive Agents MeSH
- Atrasentan MeSH
- Bosentan MeSH
- Endothelin-1 MeSH
- Sodium Chloride, Dietary MeSH
- Pyrrolidines MeSH
- Receptor, Endothelin A MeSH
- Receptor, Endothelin B MeSH
- Ren2 protein, mouse MeSH Browser
- Renin MeSH
- Sulfonamides MeSH
The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a monogenic model of angiotensin II-dependent hypertension with endogenous activation of the renin-angiotensin system. Homozygous males TGR develop malignant hypertension with a strong salt-sensitive component. These animals show severe hypertension, proteinuria and high mortality. Morphological changes of renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous TGR develop only mild hypertension and thus provide a more suitable model of hypertension regarding to clinical studies. Within the renal parenchyma, secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet in heterozygous animals induces transition from benign to malignant phase of hypertension. In this case, ischemic glomerular changes are superimposed on preexisting secondary FSGS. In the regression model of hypertension (late-onset treatment) the effect of salt intake is attenuated. In homozygous TGR, early selective ET(A) receptor blockade decreased blood pressure and ameliorated end-organ damage. Late selective ET(A) receptor blockade reduced podocyte injury despite final severe hypertension. Survival rate was markedly improved in both regimens with ET(A) selective blockade, while there was only partial improvement with early non-selective blockade. Both bosentan and atrasentan decreased ET-1 levels in both regimens. In heterozygous TGR, early and late ET(A) treatment substantially while ET(A)/ET(B) treatment partially improved survival rate. Significant effect on BP was found with early and late ET(A) blockade, while ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is superior to nonselective ET(A)/ET(B) receptor blockade in attenuating hypertension and end-organ damage. Its effect is more pronounced when applied early in the life.
References provided by Crossref.org
Sex differences in blood pressure of aged Ren-2 transgenic rats
